Recent studies in this laboratory have shown that silver metallic particles can have dramatic favorable effects or nearby fluorophores. These effects include increased quantum yields, multi-photon excitation, photostability absorption cross sections and longer distances for fluorescence resonance energy transfer. These studies were performed on silver island films in which the silver is bound to an inert substrate. This form is not suitable for medical applications requiring injection. We now propose to develop complexes of indocyanine green (ICG)with silver, gold or other nobel metal colloids for use as improved optical contrast agents for retinal angiography and imaging of cardiac vasculature. The Specific Aims and Milestones for Phase I are: Specific Aim 1: Develop suspensions which are complexes of ICG and silver colloids which display a 10-fold increase in ICG intensity without increases in the bulk ICG concentration. Specific Aim 2: Use the ICG-colloid complexes for retinal imaging in rabbits to obtain a 3-fold increase in ICG intensity, without acute toxic effects for the rabbits. Phase II of the project will use the experience and results of Phase I to guide further development of this new class of contrast agents. Specific Aim 1: Optimize the spectral properties of the ICG-silver complexes by controlling the ICG-to-metal distance, coupling chemistry, use of inert coating and particle size. Specific Aim 2: Evaluate the use of other metallic colloids including gold, platinum and palladium Specific Aim 3: Evaluate the use of the ICG-colloids in the rabbit eye model for improved imaging and differential imaging of choroid circulation. Specific Aim 4: Extend the use of ICG-metal colloid complexes for imaging of cardiac vasculature.